The long term objective of this program is to elucidate the intrinsic regulatory mechanisms that control the structure and function of the articular cartilage that normally protects and cushions underlying bones. We recently showed that TGF-~ has the ability to prevent the spontaneous proteoglycan loss that occurs in basal cartilage organ cultures. We have now studied the effect of TGF-beta on the articular cartilage matrix and demonstrated that this effector is a powerful antagonist of the resorbing action of vitamin A (retinoic acid) on matrix proteoglycans. These findings extend our basic knowledge of the regulatory mechanisms that maintain cartilage matrix structure and function. This kind of fundamental information is critical to understand and eventually manage joint diseases that involve aberrant metabolism of articular cartilage matrix, such as occurs in osteoarthritis.